A mass spectrometer with a novel multipoint field ionization source, which has been constructed in the first phase of this program, will be used in conjunction with thin layer and gas-liquid chromatography to extend the methodologies of tracer analysis and isotope dilution analysis to molecules multilabeled with stable isotopes. The overall sensitivity of the technique is sufficient to detect 10 to the minus 12th power g or less of multilabeled molecular tracers with a precision of plus or minus 1%. This would facilitate the determination of labeled drug or metabolite concentrations in 1 microgram of tissue. A sample this small could be readily obtained by needle biopsy. Using molecular tracers as the major component in dilution analysis is possible to asses 10 to the minus 12th power g or less of specific unlabeled metabolites or drugs. Using this methodology it will be possible to assess directly (1) the success of oncological treatment by following the diminution of uptake of labeled metabolites such as thymidine or uridine or the diminution in the rate of formation of polyamines; and (2) the uptake of chemotherapeutic drugs such as cyclophisphoamide, 5-fluorouracil hydroxyurea, araclinose cytosine, etc. by malignant and by normal tissues. Within the framework of the program, multilabeled drugs and metabolites will be synthesized and used in vivo as tracers or isotopic dilutants in cancer diagnosis and cancer therapy. A cooperative effort with a number of clinicians has been initiated to apply the developed techniques to actual clinical studies.